LPS-neutralizing peptides reduce outer membrane vesicle-induced inflammatory responses.

Outer membrane vesicles (OMVs) are secreted by Gram-negative bacteria and induce a stronger inflammatory response than pure LPS. After endocytosis of OMVs by macrophages, lipopolysaccharide (LPS) is released from early endosomes to activate its intracellular receptors followed by non-canonical inflammasome activation and pyroptosis, which are critically involved in sepsis development. Previously, we could show that the synthetic anti-endotoxin peptide Pep19-2.

Intracellular Lipopolysaccharide Sensing as a Potential Therapeutic Target for Sepsis.

Lipopolysaccharide (LPS) sensing in the cytosol by the noncanonical inflammasome leads to pyroptosis and NLRP3 inflammasome activation. This mechanism may be more critical for sepsis development than recognition of LPS by Toll-like receptor 4. LPS is directly binding to its intracellular receptor caspase-4/5/11, mediated by outer membrane vesicles and guanylate-binding proteins that deliver LPS to the cytosol and mediate access of caspases to LPS.

Antimicrobial endotoxin-neutralizing peptides promote keratinocyte migration via P2X7 receptor activation and accelerate wound healing in vivo.

Background And Purpose: Wound healing is a complex process that is essential to provide skin homeostasis. Infection with pathogenic bacteria such as Staphylococcus aureus can lead to chronic wounds, which are challenging to heal. Previously, we demonstrated that the antimicrobial endotoxin-neutralizing peptide Pep19-2.

Antimicrobial Peptides and Their Therapeutic Potential for Bacterial Skin Infections and Wounds.

Alarming data about increasing resistance to conventional antibiotics are reported, while at the same time the development of new antibiotics is stagnating. Skin and soft tissue infections (SSTIs) are mainly caused by the so called ESKAPE pathogens (, and species) which belong to the most recalcitrant bacteria and are resistant to almost all common antibiotics. and are the most frequent pathogens isolated from chronic wounds and increasing resistance to topical antibiotics has become a major issue.

Synthetic anti-endotoxin peptides inhibit cytoplasmic LPS-mediated responses.

Toll-like receptor (TLR) 4-independent recognition of lipopolysaccharide (LPS) in the cytosol by inflammatory caspases leads to non-canonical inflammasome activation and induction of IL-1 secretion and pyroptosis. The discovery of this novel mechanism has potential implications for the development of effective drugs to treat sepsis since LPS-mediated hyperactivation of caspases is critically involved in endotoxic shock. Previously, we demonstrated that Pep19-2.

Cell type-specific regulatory effects of glucocorticoids on cutaneous TLR2 expression and signalling.

Glucocorticoids (GCs) induce Toll-like receptor (TLR) 2 expression and synergistically upregulate TLR2 with pro-inflammatory cytokines or bacteria. These paradoxical effects have drawn attention to the inflammatory initiating or promoting effects of GCs, as GC treatment can provoke inflammatory skin diseases. Here, we aimed to investigate the regulatory effects of GCs in human skin cells of different epidermal and dermal layers.

Synthetic antimicrobial and LPS-neutralising peptides suppress inflammatory and immune responses in skin cells and promote keratinocyte migration.

The stagnation in the development of new antibiotics and the concomitant high increase of resistant bacteria emphasize the urgent need for new therapeutic options. Antimicrobial peptides are promising agents for the treatment of bacterial infections and recent studies indicate that Pep19-2.5, a synthetic anti-lipopolysaccharide (LPS) peptide (SALP), efficiently neutralises pathogenicity factors of Gram-negative (LPS) and Gram-positive (lipoprotein/-peptide, LP) bacteria and protects against sepsis.

Sphingosine 1-phospate differentially modulates maturation and function of human Langerhans-like cells.

Background: As mediators between innate and adaptive immune responses, Langerhans cells (LCs) are in the focus of recent investigations to determine their role in allergic inflammatory diseases like allergic contact dermatitis and atopic dermatitis. Sphingosine 1-phosphate (S1P) is a crucial lipid mediator in the skin and potentially interferes with LC homeostasis but also functional properties, such as cytokine release, migration and antigen-uptake which are considered to be key events in the initiation and maintenance of pathological disorders.

Objective: Here, we used human Langerhans-like cells to study the influence of S1P-mediated signalling on LC maturation, cytokine release, migration and endocytosis.